Sodium borohydride → Ethyl 4-cyano-3-[1-(3,4-dichlorophenyl)-3-hydroxypropyl]-5-(morpholin-4-yl)thiophene-2-carboxylate

HRID 2402154Notes

Reaction equation

HRID 2402154 reaction equation
[C:1]([C:3]1[C:4]([CH:19]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=2)[CH2:20][CH:21]=[O:22])=[C:5]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[S:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)#[N:2].[BH4-].[Na+]>C(O)C>[C:1]([C:3]1[C:4]([CH:19]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=2)[CH2:20][CH2:21][OH:22])=[C:5]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[S:6][C:7]=1[N:8]1[CH2:9][CH2:10][O:11][CH2:12][CH2:13]1)#[N:2]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 86667483Ethyl 4-cyano-3-[1-(3,4-dichlorophenyl)-3-oxopropyl]-5-(morpholin-4-yl)thiophene-2-carboxylate

Product 1

HCID 66747681Ethyl 4-cyano-3-[1-(3,4-dichlorophenyl)-3-hydroxypropyl]-5-(morpholin-4-yl)thiophene-2-carboxylateYield 75.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of ethyl 4-cyano-3-[1-(3,4-dichlorophenyl)-3-oxopropyl]-5-(morpholin-4-yl)thiophene-2-carboxylate (50.0 mg, 0.107 mmol) in ethanol (1.00 mL) was added sodium tetrahydroborate (4.05 mg, 0.107 mmol). The mixture was stirred at rt for 1 hr. The reaction was quenched with 1.00 M of hydrochloric acid in water (0.428 mL) and distributed between NaHCO3(aq) saturated solution and EtOAc. The aqueous layer was extracted with EtOAc (×2). The combined organic layer was dried and concentrated to provide a white solid. Purification on a silica gel column (gradient elution 0-5% MeOH) provided ethyl 4-cyano-3-[1-(3,4-dichlorophenyl)-3-hydroxypropyl]-5-(morpholin-4-yl)thiophene-2-carboxylate as a colorless syrup (38 mg, 75.7% yield). 1H NMR (400 MHz, CDCl3) δ 7.46-7.35 (dd, J=5.2, 3.1 Hz, 2H), 7.30-7.19 (m, 1H), 5.65-5.52 (t, J=8.0 Hz, 1H), 4.42-4.26 (q, J=7.1 Hz, 2H), 3.85-3.77 (t, J=4.9 Hz, 4H), 3.76-3.65 (ddt, J=13.0, 9.0, 4.6 Hz, 1H), 3.57-3.44 (t, J=4.8 Hz, 5H), 2.69-2.58 (dd, J=8.4, 4.1 Hz, 1H), 2.56-2.43 (dt, J=8.1, 4.9 Hz, 2H), 1.44-1.32 (t, J=7.1 Hz, 3H).

Workup

  1. customThe reaction was quenched with 1.00 M of hydrochloric acid in water (0.428 mL)
  2. extractionThe aqueous layer was extracted with EtOAc (×2)
  3. customThe combined organic layer was dried
  4. concentrationconcentrated
  5. customto provide a white solid
  6. customPurification
  7. washon a silica gel column (gradient elution 0-5% MeOH)

Sources & evidence

ORD record
ord-19def901654041868f789bb2367710d9
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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